Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus.

Carmines, Pamela K.; Ohishi, Kentaro; Ikenaga, Hideki

doi:10.1172/jci119075

Cited by 67 publications

(46 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30 Because these channels are prominent in the renal afferent arteriole 9,10 and in evoking the vasoconstrictor response of this vessel to Ang II, 8 we assessed the impact of AG18 on K ] and constrictor responses to this maneuver are blocked by nifedipine and diltiazem. 9,31 In contrast with the behavior of nonrenal vascular beds, 6,32-34 tyrosine kinase blockade did not alter K ϩ -induced afferent arteriolar constriction in the present study. This observation has several mechanistic implications.…”

Section: Carmines Et Al Tyrosine Kinase and Renal Arteriolar Constriccontrasting

confidence: 70%

Tyrosine Kinase Involvement in Renal Arteriolar Constrictor Responses to Angiotensin II

et al. 2001

View full text Add to dashboard Cite

Abstract-Experiments were performed to test the hypothesis that tyrosine kinase activity contributes to renal arteriolar contractile responses to angiotensin (Ang) II. Rats were subjected to short-term enalaprilat treatment to decrease endogenous Ang II formation before tissue was harvested for experiments with the in vitro blood-perfused juxtamedullary nephron technique. Acute surgical papillectomy was used to avoid the indirect afferent arteriolar effect of Ang II that arises through increased tubuloglomerular feedback sensitivity. Arteriolar lumen diameter responses to 1 and 10 nmol/L Ang II were monitored by videomicroscopic methods before and during treatment with various tyrphostin compounds: 100 mol/L AG18 (broad-spectrum tyrosine kinase inhibitor), 100 nmol/L AG1478 (selective epidermal growth factor receptor tyrosine kinase inhibitor), or 100 mol/L AG9 (inactive analog). Baseline afferent arteriolar lumen diameter averaged 23.5Ϯ1.2 m and was not influenced by any tyrphostin. Ang II (10 nmol/L) decreased afferent diameter by 11.1Ϯ1.0 m under untreated conditions, a response that was not altered by AG9 but significantly blunted by AG18 (34Ϯ9% inhibition) or AG1478 (52Ϯ8% inhibition). AG18 did not suppress afferent arteriolar contractile responses to membrane depolarization (20 to 55 mmol/L K ϩ bath). Efferent arteriolar baseline diameter averaged 24.1Ϯ0.8 m and was unaltered by AG18 or AG1478; however, efferent diameter responses to 10 nmol/L Ang II were diminished 52Ϯ10% by AG18 and 51Ϯ13% by AG1478. These observations indicate that Ang II signaling in renal afferent and efferent arteriolar vascular smooth muscle is either mediated or modulated by tyrosine kinase activity, including that of the epidermal growth factor receptor tyrosine kinase.

show abstract

Section: Carmines Et Al Tyrosine Kinase and Renal Arteriolar Constriccontrasting

confidence: 70%

Tyrosine Kinase Involvement in Renal Arteriolar Constrictor Responses to Angiotensin II

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Abnormal TGF responsiveness has been reported previously in diabetes, especially in insulin-deficient states (8,27). In addition, a dysfunction of voltage-dependent Ca 2ϩ channels in vascular smooth muscle cells or an increased activation of ATP-dependent K ϩ channels has been reported, suggesting that myogenic reactivity may be abnormal in diabetes as well (3). The diminished stability of RBF in the face of changes of RPP in STZ-induced diabetes in rats has been found to be improved by treatment with insulin (2, 5).…”

Section: Discussionmentioning

confidence: 80%

Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats

Hashimoto¹,

Yamada²,

Kawata³

et al. 2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The mechanisms underlying the development and prevention of diabetic nephropathy are still not fully understood. In the present study in the Otsuka Long-Evans Tokushima Fatty (OLETF) model of type 2 diabetic rats, we investigated whether renal hemodynamic abnormalities exist and whether they precede the onset of diabetes. Using OLETF rats in both prediabetic and diabetic stages, we assessed autoregulatory responses of total renal blood flow (RBF) and of superficial (SBF) and deep renal cortical (DBF) blood flow to stepwise reductions of renal perfusion pressure (RPP) induced by a manual clamp on the abdominal aorta. During clamp-induced reductions of RPP by 10 or 20 mmHg, RBF fell significantly more in OLETF rats than in lean control [Long-Evans Tokushima Otsuka (LETO)] rats. Whereas SBF showed no significant changes in either OLETF rats or LETO rats during mild clamping, DBF decreased significantly more in OLETF rats than LETO rats. Reduced autoregulatory efficiency in OLETF rats was observed in both prediabetic and diabetic stages. Micropuncture studies showed that tubuloglomerular feedback (TGF) responses of stop flow pressure are reduced in prediabetic (Ϫ7.3 vs. Ϫ25.7%) as well as in diabetic OLETF rats compared with LETO control rats (Ϫ4.4 vs. Ϫ18.8%). Renal corticotomy was performed to measure glomerular capillary pressure (P gc) directly. P gc of deep cortical glomeruli was higher than superficial glomerular P gc in both strains of rats, but the difference was especially pronounced in OLETF rats (deep 78 Ϯ 2 vs. superficial 57 Ϯ 4 mmHg). This study demonstrates reduced autoregulatory adjustments and impaired TGF efficiency in prediabetic OLETF rats. Thus abnormal RBF regulation precedes the onset of diabetes and is especially pronounced in the deep cortical region.

show abstract

“…Paradoxically, the effects of diabetes on VDCC function in the circulatory system are variable. On the one hand, arteriolar L-type VDCC activity is attenuated in the kidney 30 and tail 31 of diabetic rats. On the other hand, VDCC activity appears to be increased in mesenteric, 32 skeletal, 33 and cerebral 34 arteriolar myocytes.…”

Section: Discussionmentioning

confidence: 99%

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Matsushita

Fukumoto

Kobayashi

et al. 2010

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE.Although decentralized control of blood flow is particularly important in the retina, knowledge of the functional organization of the retinal microvasculature is limited. Here, the authors characterized the distribution and regulation of L-type voltage-dependent calcium channels (VDCCs) within the most decentralized operational complex of the retinal vasculature-the feeder vessel/capillary unit-which consists of a capillary network plus the vessel linking it with a myocyteencircled arteriole. METHODS. Perforated-patch recordings, calcium-imaging, and time-lapse photography were used to assess VDCC-dependent changes in ionic currents, intracellular calcium, abluminal cell contractility, and lumen diameter, in microvascular complexes freshly isolated from the rat retina. RESULTS. Topographical heterogeneity was found in the distribution of functional VDCCs; VDCC activity was markedly greater in feeder vessels than in capillaries. Experiments showed that this topographical distribution occurs, in large part, because of the inhibition of capillary VDCCs by a mechanism dependent on the endogenous polyamine spermine. An operational consequence of functional VDCCs predominantly located in the feeder vessels is that voltage-driven vasomotor responses are generated chiefly in this portion of the feeder vessel/capillary unit. However, early in the course of diabetes, this ability to generate voltage-driven vasomotor responses becomes profoundly impaired because of the inhibition of feeder vessel VDCCs by a spermine-dependent mechanism. CONCLUSIONS. The regulation of VDCCs by endogenous spermine not only plays a critical role in establishing the physiological organization of the feeder vessel/capillary unit, but also may contribute to dysfunction of this decentralized operational unit in the diabetic retina. (Invest Ophthalmol Vis Sci.

show abstract

Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus.

Cited by 67 publications

References 57 publications

Tyrosine Kinase Involvement in Renal Arteriolar Constrictor Responses to Angiotensin II

Tyrosine Kinase Involvement in Renal Arteriolar Constrictor Responses to Angiotensin II

Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Contact Info

Product

Resources

About